Mustafa Capraz, Akin Tekcan, Mustafa Cihangiroglu, Ayse Feyda Nursal, Aylin Capraz, Elif Menekse, Hatice Dortok Demir, Nilufer Kuruca, Serbulent Yigit
{"title":"The effect of the <i>MBL2</i> gene rs1800450 variant on COVID-19 development in Turkish patients.","authors":"Mustafa Capraz, Akin Tekcan, Mustafa Cihangiroglu, Ayse Feyda Nursal, Aylin Capraz, Elif Menekse, Hatice Dortok Demir, Nilufer Kuruca, Serbulent Yigit","doi":"10.1080/15257770.2024.2395872","DOIUrl":"10.1080/15257770.2024.2395872","url":null,"abstract":"<p><p>The coronavirus disease 2019 (COVID-19) is a recent pandemic occurring worldwide due to the <i>severe acute respiratory syndrome coronavirus 2</i> (SARS-CoV-2) virus, spreading mainly through large respiratory droplets or maybe through other transmission routes. The human genome has the most varied immune response genes correlated with infectious diseases. Genetic variants of mannose-binding lectin 2 (<i>MBL2</i>), an immunomodulatory gene, were associated with the risk, severity, and frequency of viral infections. In the present study, we hypothesized that the <i>MBL2</i> gene rs1800450 variant could be associated with the development of COVID-19 disease in a Turkish population. Ninety-eight COVID-19 patients and 98 healthy, ethnically matched controls were studied. We isolated genomic DNA from whole blood and analyzed the <i>MBL2</i> rs1800450 using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Associations were analyzed with the SPSS 20 statistical software. We found that <i>MBL2</i> rs1800450 genotype distribution was significantly different between patients and controls. The patients had a higher <i>MBL2</i> rs1800450 AA genotype than the controls had (4.94% in patients vs. 3.12% in controls, <i>p</i> = 0.006). The subjects carrying AA genotype had a 10.83-fold increased risk for COVID-19 disease (OR = 10.83, %95 CI = 1.359-86.349). We could not detect any significant difference between the COVID-19 patients and healthy controls in allele frequencies. Our findings demonstrated that the <i>MBL2</i> rs1800450 BB genotype might increase the susceptibility to COVID-19 disease in the Turkish population. We suggest further studies with a larger sample size and other ethnic populations.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"79-89"},"PeriodicalIF":1.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142109977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Association between <i>ACE</i> (rs4343 and rs1799752), <i>AGTR1</i> (rs5186), and <i>PAI-1</i> (rs2227631) polymorphisms in the host and the severity of Covid-19 infection.","authors":"Seher Polat, Zühal Özer Şimşek","doi":"10.1080/15257770.2024.2387033","DOIUrl":"10.1080/15257770.2024.2387033","url":null,"abstract":"<p><strong>Objective: </strong>It is necessary to identify appropriate clinical, biochemical, epidemiological and genetic biomarkers to elucidate the underlying mechanisms of the coronavirus disease-2019 (COVID-19) disease. The study focused on not only the link between disease severity (non-intense unit care (non-ICU) versus intensive unit care (ICU) and genetic susceptibility in COVID-19 patients but also the connection between comorbidity and genetic susceptibility affecting the severity of COVID-19.</p><p><strong>Subject and methods: </strong>One hundred and sixty-two COVID-19 patients treated in the non-ICU and ICU in Kayseri City Hospital were included. All volunteers underwent a physical examination and biochemical evaluation. Angiotensin-converting enzyme (<i>ACE</i> p.T776T G > A(rs4343) and g.16471_16472delinsALU (also referred to as I/D polymorphism; rs1799752), angiotensin II receptor type-1 (<i>AGTR1)</i> c.*86A > C (also referred to as A1166C; rs5186), and plasminogen activator inhibitor-1 (<i>PAI-1</i>-844 G > A (rs2227631) polymorphisms were analysed as well.</p><p><strong>Results: </strong>To have ACE \"ID\" genotype did not change the severity of the disease (OR: 0.92, 95% CI: 0.41-2.1, <i>p</i> = 0.84), but decreased the mortality risk 2.9-fold (OR: 2.9, 95% CI: 1.1-7.0, <i>p</i> = 0.03). In <i>PAI-1</i>-844 G > A, having the \"AA\" genotype in the \"A\" recessive model increased the risk of the diabetes mellitus (DM) 2.3-fold (OR: 2.3 95%, CI: 1.16-4.66, <i>p</i> = 0.018). In the \"G\" recessive model, to have the GG genotype increased the risk of chronic kidney disease (CKD) 4.8-fold (OR:4.8, 95% CI: 1.5-15.5, <i>p</i> = 0.008). \"GG\" genotype in the DM group had a higher fibrinogen level compared to those with the \"AG\" genotype (AG:4847.2 mg/L (1704.3) versus GG:6444.67 mg/L (1861.62) <i>p</i> = 0.019) and \"AA\" genotype in the CKD group had lower platelet levels and those with \"GG\" had higher platelet levels (AA:149 µL (18-159) versus GG: 228 µL (146-357) <i>p</i> = 0.022).</p><p><strong>Conclusion: </strong>This study was shown that genetic predispositions that causes comorbidities were also likely to affect the prognosis of COVID-19.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"57-78"},"PeriodicalIF":1.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141875520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Özgür Ülkü Özdemir, Kübra Yurt, Ayşe Nur Pektaş, Şeyda Berk
{"title":"Evaluation and normalization of a set of reliable reference genes for quantitative <i>sgk-1</i> gene expression analysis in <i>Caenorhabditis elegans</i>-focused cancer research.","authors":"Özgür Ülkü Özdemir, Kübra Yurt, Ayşe Nur Pektaş, Şeyda Berk","doi":"10.1080/15257770.2024.2317413","DOIUrl":"10.1080/15257770.2024.2317413","url":null,"abstract":"<p><p>Multiple signaling pathways have been discovered to play a role in aging and longevity, including the insulin/IGF-1 signaling system, AMPK pathway, TOR signaling, JNK pathway, and germline signaling. Mammalian serum and glucocorticoid-inducible kinase 1 (<i>sgk-1</i>), which has been associated with various disorders including hypertension, obesity, and tumor growth, limits survival in <i>C. elegans</i> by reducing DAF-16/FoxO activity while suppressing FoxO3 activity in human cell culture. <i>C. elegans</i> provides significant protection for a number of genes associated with human cancer. The best known of these are the <i>lin-35/pRb</i> (mammalian ortholog <i>pRb</i>) and CEP-1 (mammalian ortholog <i>p53</i>) genes. Therefore, in this study, we aimed to investigate the expression analyzes of <i>sgk-1</i>, which is overexpressed in many types of mammalian cancer, in mutant lin-35 and to demonstrate the validation of reference genes in wild-type N2 and mutant lin-35 for <i>C. elegans</i>-focused cancer research. To develop functional genomic studies in <i>C. elegans</i>, we evaluated the expression stability of five candidate reference genes (<i>act-1, ama-1, cdc-42, pmp-3</i>, <i>iscu-1</i>) by quantitative real-time PCR using five algorithms (geNorm, NormFinder, Delta Ct method, BestKeeper, RefFinder) in N2 and lin-35 worms. According to our findings, <i>act-1</i> and <i>cdc-42</i> were effective in accurately normalizing the levels of gene expression in N2 and lin-35. <i>act-1</i> and <i>cdc-42</i> also displayed the most consistent expression patterns, therefore they were utilized to standardize expression level of <i>sgk-1</i>. Furthermore, our results clearly showed that <i>sgk-1</i> was upregulated in lin-35 worms compared to N2 worms. Our results highlight the importance of definitive validation using mostly expressed reference genes.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"91-110"},"PeriodicalIF":1.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139741536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gulcin Ozkara, Ezgi Irmak Aslan, Ayse Begum Ceviz, Gonca Candan, Fidan Malikova, Allison Pinar Eronat, Ozgur Selim Ser, Onur Kılıcarslan, Ozlem Kucukhuseyin, Cem Bostan, Ahmet Yildiz, Oguz Ozturk, Hulya Yilmaz-Aydogan
{"title":"Unusual effects of <i>PCSK9 E670G</i> (rs505151) variation in patients with in-stent restenosis: Variable effects on restenosis risk according to concomitant chronic conditions.","authors":"Gulcin Ozkara, Ezgi Irmak Aslan, Ayse Begum Ceviz, Gonca Candan, Fidan Malikova, Allison Pinar Eronat, Ozgur Selim Ser, Onur Kılıcarslan, Ozlem Kucukhuseyin, Cem Bostan, Ahmet Yildiz, Oguz Ozturk, Hulya Yilmaz-Aydogan","doi":"10.1080/15257770.2024.2316724","DOIUrl":"10.1080/15257770.2024.2316724","url":null,"abstract":"<p><p>Recent reports showing that neo-atherosclerosis formation in stented coronary artery is characterized by the accumulation of lipid-laden macrophages within the neointima has strengthened the possibility that elevated low-density lipoprotein (LDL)-cholesterol may be a risk factor for in-stent restenosis (ISR). Protein Convertase Subtilisin/Kexin-9 (PCSK9) protein plays an important role in cholesterol metabolism by degrading of LDL receptors. The gain-of-function <i>E670G</i> (rs505151) mutation of the <i>PCSK9</i> gene is a well-known genetic risk factor for hypercholesterolemia. This study evaluated for the first time the association of the <i>E670G</i> variation with the serum lipids, PCSK9 levels and concomitant diseases on the ISR risk. The study included 109 ISR, and 82 Non-ISR patients, based on the results of coronary angiography. Genotypes were determined using the real-time PCR and serum PCSK9 levels were measured by ELISA technique. The rare G allele of <i>PCSK9 E670G</i> (<i>p</i> < 0.05), hyperlipidemia (HL) (<i>p</i> < 0.001), and type 2 diabetes (T2DM) (<i>p</i> < 0.01) were associated with increased risk for ISR. In hyperlipidemic conditions, the <i>E670G</i>-G allele was associated with hypercholesterolemia and a higher risk of ISR (<i>p</i> < 0.001), while the <i>E670G-</i>AA genotype has been associated with a high prevalence of T2DM and hypertension. In addition, diabetic ISRs had higher serum PCSK9 levels (<i>p</i> < 0.05) and the <i>E670G</i>-AA genotype was associated with increased levels of diabetes markers. Our results indicated that the unusual effects of both G allele and AA genotype of the <i>PCSK9 E670G</i> variation may be involved in the risk of ISR in association with concomitant metabolic diseases.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"185-205"},"PeriodicalIF":1.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139741538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"<i>MEG3</i> rs7158663 genetic polymorphism is associated with the risk of hepatocellular carcinoma.","authors":"Yong Wang, Fulei Gao, Jian Lu","doi":"10.1080/15257770.2024.2350513","DOIUrl":"10.1080/15257770.2024.2350513","url":null,"abstract":"<p><p>Recently, a meta-analysis has shown that a potentially functional genetic polymorphism (rs7158663 A > G) on the cancer-associated lncRNA MEG3 is associated with the risk of many types of cancer. Given the important role of MEG3 in the development of hepatocellular carcinoma (HCC), the current study evaluated the association of the rs7158663 genetic polymorphism with HCC risk. A total of 271 HCC patients and 267 healthy individuals were included in the current case-control study. Direct sequencing was used to detect the rs7158663 locus genotype of the included individuals. The case-control study showed that the <i>MEG3</i> rs7158663 genetic polymorphism was associated with the increased risk of developing HCC [GA vs. GG: OR = 1.63, 95% CI = 1.14-2.34, <i>p</i> = 0.009; AA vs. GG: OR = 2.10, 95% CI = 1.10-4.08, <i>p</i> = 0.03; (GA + AA) vs. GG: OR = 1.70, 95% CI = 1.21-2.40, <i>p</i> = 0.003; A vs. G: OR = 1.53, 95% CI = 1.17-2.00, <i>p</i> = 0.002]. In addition, the genotype-tissue expression showed that the rs7158663 AA or GA genotype was associated with reduced MEG3 expression. Bioinformatic analysis showed that the rs7158663 genetic polymorphism not only affects the binding of transcription factors but also interacts with multiple genes through chromatin loops. In summary, the current findings suggest that the rs7158663 genetic polymorphism affecting MEG3 expression is associated with HCC risk and may serve as a marker of genetic susceptibility to HCC. However, the specific molecular mechanisms of the rs7158663 genetic polymorphism in the development of HCC need to be further revealed.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"531-541"},"PeriodicalIF":1.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140904739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sahar Torki, Masoumeh Nezhadali, Mehdi Hedayati, Helma Karimi, S Adeleh Razavi, Leila Najd Hassan Bonab
{"title":"The role of rs2236242 at SERPINA12 gene and vaspin level on papillary thyroid carcinoma.","authors":"Sahar Torki, Masoumeh Nezhadali, Mehdi Hedayati, Helma Karimi, S Adeleh Razavi, Leila Najd Hassan Bonab","doi":"10.1080/15257770.2024.2354427","DOIUrl":"10.1080/15257770.2024.2354427","url":null,"abstract":"<p><p>Several studies showed that adipokines are associated with types of cancer which are documented to be effective in cancer biology. This study aimed to determine the relationship between vaspin rs2236242 polymorphism and the vaspin level with papillary thyroid carcinoma (PTC), and multinodular goiter (MNG). In this cross-sectional study, we recruited 170 candidates. Ninety patients with newly diagnosed (PTC 60 patients and MNG 30 patients), and 80 participants as a control group referred to Shariati Hospital, Tehran, Iran, were enrolled in the study. The vaspin hormone measurements were conducted utilizing the Elisa Kit. Using Tetra amplification resistant-mutation system polymerase chain reaction (T-ARMS-PCR), the genotype of single nucleotide polymorphism (SNP) rs2236242 was determined. The statistical analysis was performed using SPSS software version 20. Our findings showed significant age and genotype frequency differences in three groups (<i>p</i>-value < 0.05). There was no significant difference in vaspin levels between PTC, and control groups. The level of vaspin in MNG compared to the control group had significantly different, but there were no differences after adjustment for age. Results showed the genotypes of vaspin rs2236242 polymorphism are not associated with the level of vaspin. The genotypes and allele frequencies of vaspin rs2236242 in the PTC and MNG groups were significant compared to the control group. We have found vaspin rs2236242 gene polymorphism as a potential marker of papillary thyroid cancer. The A allele of the vaspin SNP rs2236242 plays a protective role against PTC and MNG. SNP at rs2236242 was not significantly associated with vaspin levels.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"542-553"},"PeriodicalIF":1.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141088134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jennifer J Wanat, Jennifer J McCann, Mark Tingey, Jessica Atkins, Corinne O Merlino, Julia Y Lee-Soety
{"title":"Yeast Npl3 regulates replicative senescence outside of TERRA R-loop resolution and co-transcriptional processing.","authors":"Jennifer J Wanat, Jennifer J McCann, Mark Tingey, Jessica Atkins, Corinne O Merlino, Julia Y Lee-Soety","doi":"10.1080/15257770.2024.2374023","DOIUrl":"10.1080/15257770.2024.2374023","url":null,"abstract":"<p><p>Eukaryotic cells without telomerase experience progressively shorter telomeres with each round of cell division until cell cycle arrest is initiated, leading to replicative senescence. When yeast <i>TLC1,</i> which encodes the RNA template of telomerase, is deleted, senescence is accompanied by increased expression of TERRA (non-coding telomere repeat-containing RNA). Deletion of Npl3, an RNA-processing protein with telomere maintenance functions, accelerates senescence in <i>tlc1Δ</i> cells and significantly increases TERRA levels. Using genetic approaches, we set out to determine how Npl3 is involved in regulating TERRA expression and maintaining telomere homeostasis. Even though Npl3 regulates hyperrecombination, we found that Npl3 does not help resolve RNA:DNA hybrids formed during TERRA synthesis in the same way as RNase H1 and H2. Furthermore, Rad52 is still required for cells to escape senescence by telomere recombination in the absence of Npl3. Npl3 also works separately from the THO/TREX pathway for processing nascent RNA for nuclear export. However, deleting Dot1, a histone methyltransferase involved in tethering telomeres to the nuclear periphery, rescued the accelerated senescence phenotype of <i>npl3Δ</i> cells. Thus, our study suggests that Npl3 plays an additional role in regulating cellular senescence outside of RNA:DNA hybrid resolution and co-transcriptional processing.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"486-506"},"PeriodicalIF":1.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141559355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Downregulation of MGLL and microRNAs (miR-302b-5p, miR-190a-3p, miR-450a-2-3p) in non-small cell lung cancer: potential roles in pathogenesis.","authors":"Cilem Ozdemır, Ozgur Ilhan Celık, Arife Zeybek, Tugba Suzek, Younes Aftabı, Sevim Karakas Celık, Tuba Edgunlu","doi":"10.1080/15257770.2024.2439904","DOIUrl":"https://doi.org/10.1080/15257770.2024.2439904","url":null,"abstract":"<p><p>Genes involved in lipid metabolism have been considered potential therapeutic targets in lung cancer because lipid metabolism is severely disrupted in this cancer. Monoglyceride lipase (MGLL) is a lipolytic enzyme that converts monoacylglycerides to fatty acids and glycerol. MicroRNAs (miRNA), one of the most important epigenetic regulators of gene expression, are also considered potential biomarkers in diagnosing, treating, and prognosis lung cancer. This study aimed to investigate the potential effects of MGLL and related miRNAs (miR-302b-5p, miR-190a-3p, miR-450a-2-3p) in the pathogenesis of non-small cell lung cancer (NSCLC) by examining their expression levels and regulatory mechanisms. We analysed the expression levels of MGLL and miRNAs in 30 NSCLC and 20 non-cancerous tissues by qPCR. We performed in silico analyses to determine the biological functions of MGLL and miRNAs in NSCLC. A protein-protein interaction (PPI) network was constructed for MGLL, and gene ontology (GO) analysis, and the interacting genes were analysed using the TCGAnalyzer tool. Our study showed that the expression levels of MGLL, miR-302b-5p, miR-190a-3p and miR-450a-2-3p were significantly decreased in NSCLC tissues (<i>p</i> < 0.05). Also, according to TCGAnalyzer, MSRB3, HTR4, and FCER1G genes were downregulated genes for NSCLC. We showed that miR-302b-5p, miR-190a-3p, and miR-450a-2-3p significantly regulate the TGF-β signalling pathway. In conclusion, this study provides evidence for the potential role of MGLL and microRNAs (miR-302b-5p, miR-190a-3p, miR-450a-2-3p) in NSCLC. In subsequent studies, it was determined that MSRB3, FCER1G and LTB4R2 genes, especially the HTR4 gene, could be potential target genes for lung cancer.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"1-17"},"PeriodicalIF":1.1,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Convenient syntheses of isotopically labeled pyrimidine 2'-deoxynucleosides and their 5-hydroxy oxidation products.","authors":"Yixuan Gao, Eric T Kool","doi":"10.1080/15257770.2024.2437038","DOIUrl":"10.1080/15257770.2024.2437038","url":null,"abstract":"<p><p>Hydrolytic and oxidative damage to pyrimidine nucleobases in DNA represents a significant source of mutations in the human genome. To better understand how these lesions are incorporated and repaired in human cells, it is desirable to have ready access to isotopically enriched nucleosides for use in isotope tracing and mass spectrometry-based quantification experiments. Here we report on improved syntheses of deoxyuridine, deoxycytidine, 5-hydroxydeoxyuridine, and 5-hydroxydeoxycytidine nucleosides labeled with <sup>13</sup>C and <sup>15</sup>N. Deoxyuridine was synthesized from uracil in a direct glycosylation reaction with excellent stereoselectivity without the need to reduce a ribonucleoside intermediate. Deoxyuridine was further converted to deoxycytidine using mild O4 activation conditions with high efficiency. Finally, we document the synthetic details of preparative oxidation of deoxyuridine and deoxycytidine to their 5-hydroxy counterparts. Overall, our protocols avoid hazardous reagents and tedious conditions found in previous methods.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"1-23"},"PeriodicalIF":1.1,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12146429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"System biology analysis of miRNA-gene interaction network reveals novel drug targets in breast cancer.","authors":"Jing Huang, Yichun Gao, Jipan Liu, Zhiyuan Yang, Xiaoli Zhang","doi":"10.1080/15257770.2024.2436421","DOIUrl":"https://doi.org/10.1080/15257770.2024.2436421","url":null,"abstract":"<p><p>Breast cancer is a heterogeneous disease that is ranked as one of the most common cancers worldwide. Currently, although there are existing molecules such as progesterone receptor and estrogen receptor for breast cancer treatment, discovering more effective drug targets is still in urgent need. In this study, we have obtained six sequencing datasets of breast cancer from GEO database and identified a set of differentially expressed molecules, including 67 miRNAs and 133 genes. Function enrichment analysis by miRPathDB database indicated that targets of 11 miRNAs could be enriched in breast cancer pathway with a <i>p</i>-value ≤ .05. A special miRNA-gene interaction network was constructed for analysis of the progression of breast cancer. We then ranked the importance of each molecule (i.e. miRNA and gene) by their node centrality indexes in the network and selected the top 10% of molecules. The statistical analysis of these molecules showed three miRNAs (hsa-miR-1275, hsa-miR-2392, hsa-miR-3141) have significant effects on the prognosis and survival of patients. By searching for potential drugs in Drugbank database, we have identified four candidates (phenethyl isothiocyanate, amuvatinib, theophylline, trifluridine) for targeting these genes. In conclusion, we believe that these drugs and their analogs could be used in the targeted therapy of breast cancer in the future.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"1-16"},"PeriodicalIF":1.1,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}